The objectives are the design, synthesis, and evaluation of novel selective inhibitors of several steroid enzymes of androgen and estrogen biosynthesis. Such compounds are of potential use for regulation of hormonally dependent tumors, e.g. benign prostatic hypertrophy, and some forms of prostatic and mammary carcinoma. They are also of potential use for studies of the endocrine processes regulated by these enzymes, e.g. regulation of epididymal function, sperm storage and maturation in males; reproductive cycle regulation in females; and fetal or neonatal brain masculinization. The major approach entails in attempt to greatly increase the potency and specificity of such enzyme inhibition by the development of "suicide substrates" for the target enzymes. These agents contain latent alkylating groups that aree unmasked at the active site of the target enzyme when the enzyme carries out its normal catalytic function. The unmasked alkylating group can then covalently bind to the target enzyme and irreversibly inactivate it. Thus the enzyme catalyzes its own inactivation. Inhibitors of 3-alpha-hydroxysteroid dehydrogenase and delta-4-5-alpha-reductase will be evaluated in rat epididymal and prostatic homogenates, while inhibitors of armatase and 3-beta-hydroxy-steroid dehydrogenase will be evaluated with human placental microsomes. In vivo effects on male rat androgen dependent organs, and female mouse estrogen dependent organs will be measured. anti-tumor activity against estrogen dependent tumors will be measured in female rats carrying 7,12-dimethylbenz(a)-anthracene induced mammary tumors, and anti-tumor activity against androgen dependent tumors will be determined in male Copenhagen rats carrying the Dunning R3327H prostatic adenocarcinoma.